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Monday, March 23, 2015

Germline gene therapy: Frankenstein or Frankincense?

Science, like any other human enterprise, is largely reactionary. People in established positions of influence like to have their own way but perhaps even more, like their ways to stay basically the same: change is threatening. For that general reason, new ideas that promise to be transformative are often faced with reactionary opposition.

A few decades ago we had the recombinant DNA revolution. Changing DNA in bacteria for experimental reasons was seen as a potential global threat: if recombinant bacteria escaped the lab, they could become a global pandemic disaster that would make malaria or the bubonic plague seem trivial by comparison. Of course, those excited about the potential of the new method, for legitimate as well as venal reasons, pushed hard to be allowed to proceed. After careful examination, various protections were imposed (like working with experimental strains of E. coli that could not really live outside of test tubes), but these were loosened or abandoned over time, as the threats never materialized.

There are still some rumblings about this, as for example, the recent controversy over labs refusing to desist from engineering dangerous flu viruses to see what changes were needed to enable them to transfer from person to person more easily (they originate now in animals). The rationale is to anticipate such occurrences and develop preventive measures or vaccines etc. This work is on-again-off-again, in response to governmental and other dictates, and then pressure from investigators to do this no matter what, and then back again, as the issues are batted back and forth, unresolved.

A few years ago there was the reaction to cloning, when it was done to make Dolly, the sheep in a lab in Scotland. There are many issues about this process, both the sci-fi horrors of cloning armies of humans who are genetically unable to experience fear, and the fact that cloning from an adult's cell would make newborns more vulnerable to age-related diseases. Human cloning is not allowed as yet, though there are some rather similar things going on in the in vitro fertilization world to select embryos without known disease-related genetic variants. As we understand it, various types of cloning are widespread in agricultural animals.

Another example is the reaction to genetically modified organisms (GMOs) and their potential to make proteins that would turn out to be allergenic or in other ways harmful, or to damage ecosystems by altering pests infestations as well as inadvertently destroying insect pollinators, the enabling of large-scale monocropping, and so on. This debate is ongoing, and widely publicized. It has stimulated 'natural' foods, non-GMO containing foods, local sustainable agriculture, etc. Some of the resistance was, in essence, not about personal health but about the way GMOs threaten local farmers around the world, deplete natural variability, threaten bees and other pollinators, and more.

Much of the opposition to these sorts of change is emotional and sociopolitical--but that is not a criticism, because people are emotional and sociopolitical. And that applies to people on both sides of the debates: nobody can claim that the proponents of the new technologies are dispassionate and without self-interest and limited perspectives.

Human genetic engineering: a blessing like Frankincense?
There is now the beginning, or perhaps continuation, of a debate about human genetic engineering. Should it be done? What is it, exactly. One recent discussion outlines the issues. New technologies are being developed, one of which is called CRISPR, to engineer changes in specific genes in situ in cells. This is being done in cell culture and experimental animals and plants, to see what the specifically transgenic effects on them are. But the potential for genetic engineering to produce human babies that do not carry deleterious genes that there parent(s) may be known to carry hasn't been ignored--and, even better, the dangerous genes are removed from the population because when the babies themselves reproduce they only have the normal version to transmit to their children.

This is different from genetic engineering that tries to deliver therapy based on genetic methods to persons who are affected by genetically based diseases (like cystic fibrosis) or to deliver genetic changes to diseased tissues to counter the pathology. Those approaches are struggling to live up to their widespread promise, but there is little opposition that we know of to their implementation.

The resistance to germ line gene therapy seems to be that engineering of specific heritable genetic changes could backfire and generate new pathologies, monsters, or other unexpected side effects if the methods, still yet unproven and undergoing testing in lab species, don't work as precisely as their proponents claim.

An old way wise men tried to bless the human future: Frankincense therapy

But the idea of germ-line and hence permanent fixes is not at all new. It's a scientific analog, one might say, of the religious doctrine of the blessing conferred on humankind by the wise men one Christmas eve. An effort to save our patrimony from much suffering.

Selective abortion, prenatal counseling, and even IVF are now used to prevent the birth of babies that carry known dangerous variants that one or both parents may be known to carry. This has greatly reduced the incidence of thalassemia (a blood disease related to anemia) in Sardinia, and of Tay Sachs disease in Ashkenazi Jews, and there are likely many examples we just haven't heard about. There are now two- and even recently three-parent IVF conceptions being constructed.

So this time, the reactionary response to a new idea does seem to be reactionary. It isn't that there's no risk of horrible misadventures occurring if the new techniques fail, and it's fair enough to say this should be stopped cold until the techniques are reliable (or early enough tests available to do instantaneous aborting of dysgenic conceptuses). But that is not the same as reacting to the idea of germ-line therapy in the first place as if it were new in concept.

To prevent Frankensteins?
There will, of course, be those who agree with all of this so far, but foresee the mis-use of the procedure by rogue elements or governments for example to create fearless soldiers, drones, slaves, and so on based on mass-scale genetic engineering of this type. Or doing the same kind of thing to create super-plagues (e.g., to visit on enemies). Rogue elements can be expected to arise here and there within governments (e.g., in intelligence services, military, or other agencies).

Blessing gone awry: Boris Karloff style

Dr Frankensteins would perhaps find willing employers in such places. Some would be rogues. Some might offer their services to our enemies. Some might engineer irresistible plague germs. Such elements always exist in society. There is plenty of evidence to think that otherwise respectable scientists will be (or are) doing this covertly or will find ways, such as by leaving universities to set up companies, moving to more permissive countries, and so on, to do this and skirt regulations and restrictions.

It is also true that the same sorts of claims have been around for a long time. That the predicted disasters haven't occurred--yet--is no reason to relax vigilance. After all, the Nazi 'scientists' and 'doctors' were among the leading professionals of their days. And this sort of thing wasn't restricted to Germany in the 20th century: it was part of global eugenics thinking and actions taken against those deemed to be inherently (that is, genetically) inferior. Only a newborn babe would be so naive as to think the same sort of mentality cannot be found among today's leading scientists.

But perhaps every blessing comes with a curse, and to gain the former we must guard against the latter. While vigilance is never perfect, and risks always do exist, at least we should recognize the positive potential for removing dangerous genetic elements from human patrimony.

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